Search Results

You are looking at 1 - 10 of 14 items for

  • Author or Editor: Roy W. R. Dudley x
  • Refine by Access: all x
Clear All Modify Search
Free access

Erratum. Association of novel mutation in TRPV4 with familial nonsyndromic craniosynostosis with complete penetrance and variable expressivity

Roy W. R. Dudley

Full access

Hydrocephalus-induced neurogenic stunned myocardium and cardiac arrest in a child: completely reversed with CSF diversion

Gabriel Crevier-Sorbo, Jeffrey Atkinson, Tanya Di Genova, Pramod Puligandla, and Roy W. R. Dudley

Neurogenic stunned myocardium (NSM) is a potentially fatal cause of sudden cardiogenic dysfunction due to an acute neurological event, most commonly aneurysmal subarachnoid hemorrhage in adults. Only two pediatric cases of hydrocephalus-induced NSM have been reported. Here the authors report a third case in a 14-year-old boy who presented with severe headache, decreased level of consciousness, and shock in the context of acute hydrocephalus secondary to fourth ventricular outlet obstruction 3 years after standard-risk medulloblastoma treatment. He was initially stabilized with the insertion of an external ventricular drain and vasopressor treatment. He had a profoundly reduced cardiac contractility and became asystolic for 1 minute, requiring cardiopulmonary resuscitation when vasopressors were inadvertently discontinued. Over 1 week, his ventricles decreased in size and his cardiac function returned to normal. All other causes of heart failure were ruled out, and his impressive response to CSF diversion clarified the diagnosis of NSM secondary to hydrocephalus. He was unable to be weaned from his drain during his time in the hospital, so he underwent an endoscopic third ventriculostomy and has remained well with normal cardiac function at more than 6 months’ follow-up. This case highlights the importance of prompt CSF diversion and cardiac support for acute hydrocephalus presenting with heart failure in the pediatric population.

Open access

Endoscopic third ventriculostomy for VP shunt malfunction during the third trimester of pregnancy: illustrative case

Ahmad K. Alhaj, Tariq Al-Saadi, Marie-Noëlle Hébert-Blouin, Kevin Petrecca, and Roy W. R. Dudley

BACKGROUND

Endoscopic third ventriculostomy (ETV) is a successful procedure for treating noncommunicating hydrocephalus as an alternative to initial ventriculoperitoneal (VP) shunt placement and as a salvage procedure when a VP shunt fails. Physiological changes of pregnancy can lead to VP shunt failure and complicate the management of shunt malfunction, particularly in the third trimester.

OBSERVATIONS

The authors present a case in which an ETV was successfully used in the third trimester (31 weeks of gestation) of pregnancy for acute hydrocephalus due to VP shunt malfunction, and the patient went on to deliver a healthy baby at term; the patient remained well in the long-term follow-up. An English-language PubMed literature review revealed four cases of VP shunt failure successfully treated with an ETV in the first or second trimester but no such reports in the third trimester of pregnancy.

LESSONS

ETV appears to be a safe and effective alternative to VP shunt replacement in the late prenatal period of pregnancy.

Free access

Letter to the Editor. Is arterial spin labeling relevant in MRI-negative drug-refractory epilepsy?

Raghu Samala, Ramesh Doddamani, Manjari Tripathi, and P. Sarat Chandra

Open access

Subtle magnetic resonance imaging differences in tegmental pilocytic astrocytomas as a caution against attempting gross-total resection: illustrative cases

Tariq Al-Saadi, Steffen Albrecht, Jean-Pierre Farmer, Daniela Toffoli, Christine Saint-Martin, Nada Jabado, and Roy W. R. Dudley

BACKGROUND

Although surgery within the tegmentum of the midbrain is challenging, resection of tegmental pilocytic astrocytomas (PAs) is a standard treatment because this has been shown to outperform chemotherapy and radiotherapy in terms of long-term tumor control. Gross total resection (GTR) assisted by intraoperative neuroelectrophysiological monitoring can be achieved with a reasonable risk-to-benefit ratio, especially for well-circumscribed tumors, but careful scrutiny of magnetic resonance imaging (MRI) is critical to surgical decision making. The authors present two cases of tegmental PAs, which appeared grossly similar on MRI and were operated on via the same surgical approach using the same intraoperative adjuncts.

OBSERVATIONS

The tumors had identical histopathological and molecular diagnoses but drastically different functional outcomes for the patients, with significant long-term complications for one of the children, which the authors believe was due to a slightly more invasive nature of this tumor. The authors demonstrate subtle preoperative MRI findings that might be potential clues to a more infiltrative nature of one PA versus another and present pathological findings supporting this argument.

LESSONS

This report serves as a reminder that not all tegmental PAs can be managed by the same surgical approach. Subtle signs of infiltration may indicate that GTR should not be attempted.

Free access

Successful treatment of non-midline primary malignant germ cell tumors with yolk sac components in neonates: report of 2 cases

Alexander G. Weil, Natalie Mathews, Jean-Pierre Farmer, Christine St. Martin, Steffen Albrecht, Nada Jabado, and Roy W. R. Dudley

Here, the authors present 2 cases of nongerminomatous germ cell tumor (NGGCT): a neonate with a mixed malignant germ cell tumor, 5% yolk sac tumor (YST) and 95% immature teratoma components, originating from the right mesial temporal lobe; and a 2-month-old infant with a pure YST originating from the left middle cranial fossa. These tumors with yolk sac components, which are thought to have a poor prognosis, were successfully treated with complete tumor resection alone and subtotal tumor resection with chemotherapy, respectively. Event-free survival exceeds 5 years for each patient even though neither received radiotherapy. The authors highlight the role of radical surgery and the successful treatment of neonatal YST with aggressive resection (and chemotherapy in 1 case) while avoiding radiation therapy. They also report the very rare non-midline location of these neonatal NGGCTs and emphasize the importance of considering YSTs and mixed NGGCTs with YST components in the differential diagnosis of non-midline hemispheric or skull base tumors in newborns.

Restricted access

Short-term mortality following surgical procedures for the diagnosis of pediatric brain tumors: outcome analysis in 5533 children from SEER, 2004–2011

Todd C. Hankinson, Roy W. R. Dudley, Michelle R. Torok, Mohana Rao Patibandla, Kathleen Dorris, Seerat Poonia, C. Corbett Wilkinson, Jennifer L. Bruny, Michael H. Handler, and Arthur K. Liu

OBJECT

Thirty-day mortality is increasingly a reference metric regarding surgical outcomes. Recent data estimate a 30-day mortality rate of 1.4−2.7% after craniotomy for tumors in children. No detailed analysis of short-term mortality following a diagnostic neurosurgical procedure (e.g., resection or tissue biopsy) for tumor in the US pediatric population has been conducted.

METHODS

The Surveillance, Epidemiology and End Results (SEER) data sets identified patients ≤ 21 years who underwent a diagnostic neurosurgical procedure for primary intracranial tumor from 2004 to 2011. One- and two-month mortality was estimated. Standard statistical methods estimated associations between independent variables and mortality.

RESULTS

A total of 5533 patients met criteria for inclusion. Death occurred within the calendar month of surgery in 64 patients (1.16%) and by the conclusion of the calendar month following surgery in 95 patients (1.72%). Within the first calendar month, patients < 1 year of age (n = 318) had a risk of death of 5.66%, while those from 1 to 21 years (n = 5215) had a risk of 0.88% (p < 0.0001). By the end of the calendar month following surgery, patients < 1 year (n = 318) had a risk of death of 7.23%, while those from 1 to 21 years (n = 5215) had a risk of 1.38% (p < 0.0001). Children < 1 year at diagnosis were more likely to harbor a high-grade lesion than older children (OR 1.9, 95% CI 1.5–2.4).

CONCLUSIONS

In the SEER data sets, the risk of death within 30 days of a diagnostic neurosurgical procedure for a primary pediatric brain tumor is between 1.16% and 1.72%, consistent with contemporary data from European populations. The risk of mortality in infants is considerably higher, between 5.66% and 7.23%, and they harbor more aggressive lesions.

Free access

Long-term functional benefits of selective dorsal rhizotomy for spastic cerebral palsy

Clinical article

Roy W. R. Dudley, Michele Parolin, Bruno Gagnon, Rajeet Saluja, Rita Yap, Kathleen Montpetit, Joanne Ruck, Chantal Poulin, Marie-Andrée Cantin, Thierry E. Benaroch, and Jean-Pierre Farmer

Object

Large-scale natural history studies of gross motor development have shown that children with spastic cerebral palsy (CP) plateau during childhood and actually decline through adolescence. Selective dorsal rhizotomy (SDR) is a well-recognized treatment for spastic CP, but little is known about long-term outcomes of this treatment. The purpose of this study was to assess the durability of functional outcomes in a large number of patients through adolescence and into early adulthood using standardized assessment tools.

Methods

The authors analyzed long-term follow-up data in children who had been evaluated by a multidisciplinary team preoperatively and at 1, 5, 10, and 15 years after SDR. These evaluations included quantitative, standardized assessments of lower-limb tone (Ashworth Scale), Gross Motor Function Measure (GMFM), and performance of activities of daily living (ADLs) by the Pediatric Evaluation of Disability Inventory in children who had been stratified by motor severity using the Gross Motor Function Classification System (GMFCS). In addition, group-based trajectory modeling (GBTM) was used to identify any heterogeneity of response to SDR among these treated children, and to find which pretreatment variables might be associated with this heterogeneity. Finally, a chart review of adjunct orthopedic procedures required by these children following SDR was performed.

Results

Of 102 patients who underwent preoperative evaluations, 97, 62, 57, and 14 patients completed postoperative assessments at 1, 5, 10, and 15 years, respectively. After SDR, through adolescence and into early adulthood, statistically significant durable improvements in lower-limb muscle tone, gross motor function, and performance of ADLs were found. When stratified by the GMFCS, long-lasting improvements for GMFCS Groups I, II, and III were found. The GBTM revealed 4 groups of patients who responded differently to SDR. This group assignment was associated with distribution of spasticity (diplegia was associated with better outcomes than triplegia or quadriplegia) and degree of hip adductor spasticity (Ashworth score < 3 was associated with better outcomes than a score of 3), but not with age, sex, degree of ankle plantar flexion spasticity, or degree of hamstring spasticity. In a sample of 88 patients who had complete records of orthopedic procedures and botulinum toxin (Botox) injections, 52 (59.1%) underwent SDR alone, 11 (12.5%) received only Botox injections in addition to SDR, while 25 patients (28.4%) needed further lower-extremity orthopedic surgery after SDR.

Conclusions

In the majority of patients, the benefits of SDR are durable through adolescence and into early adulthood. These benefits include improved muscle tone, gross motor function, and performance of ADLs, as well as a decreased need for adjunct orthopedic procedures or Botox injections. The children most likely to display these long-term benefits are those in GMFCS Groups I, II, and III, with spastic diplegia, less hip adductor spasticity, and preoperative GMFM scores greater than 60.

Free access

Association of novel mutation in TRPV4 with familial nonsyndromic craniosynostosis with complete penetrance and variable expressivity

Tenzin Gayden, Gabriel Crevier-Sorbo, Wajih Jawhar, Christine Saint-Martin, Robert Eveleigh, Mirko S. Gilardino, Natascia Anastasio, Yannis Trakadis, Angelia V. Bassenden, Albert M. Berghuis, Nada Jabado, and Roy W. R. Dudley

OBJECTIVE

The aim of this study was to characterize a novel pathogenic variant in the transient receptor potential vanilloid 4 (TRPV4) gene, causing familial nonsyndromic craniosynostosis (CS) with complete penetrance and variable expressivity.

METHODS

Whole-exome sequencing was performed on germline DNA of a family with nonsyndromic CS to a mean depth coverage of 300× per sample, with greater than 98% of the targeted region covered at least 25×. In this study, the authors detected a novel variant, c.496C>A in TRPV4, exclusively in the four affected family members. The variant was modeled using the structure of the TRPV4 protein from Xenopus tropicalis. In vitro assays in HEK293 cells overexpressing wild-type TRPV4 or TRPV4 p.Leu166Met were used to assess the effect of the mutation on channel activity and downstream MAPK signaling.

RESULTS

The authors identified a novel, highly penetrant heterozygous variant in TRPV4 (NM_021625.4:c.496C>A) causing nonsyndromic CS in a mother and all three of her children. This variant results in an amino acid change (p.Leu166Met) in the intracellular ankyrin repeat domain distant from the Ca2+-dependent membrane channel domain. In contrast to other TRPV4 mutations in channelopathies, this variant does not interfere with channel activity as identified by in silico modeling and in vitro overexpression assays in HEK293 cells.

CONCLUSIONS

Based on these findings, the authors hypothesized that this novel variant causes CS by modulating the binding of allosteric regulatory factors to TRPV4 rather than directly modifying its channel activity. Overall, this study expands the genetic and functional spectrum of TRPV4 channelopathies and is particularly relevant for the genetic counseling of CS patients.

Free access

The utility of arterial spin labeling in the presurgical evaluation of poorly defined focal epilepsy in children

Jack Lam, Patricia Tomaszewski, Guillaume Gilbert, Jeremy T. Moreau, Marie-Christine Guiot, Steffen Albrecht, Jean-Pierre Farmer, Jeffrey Atkinson, Christine Saint-Martin, Pia Wintermark, Boris Bernhardt, Sylvain Baillet, and Roy W. R. Dudley

OBJECTIVE

The authors sought to assess the utility of arterial spin labeling (ASL) perfusion 3T-MRI for the presurgical evaluation of poorly defined focal epilepsy in pediatric patients.

METHODS

Pseudocontinuous ASL perfusion 3T-MRI was performed in 25 consecutive children with poorly defined focal epilepsy. ASL perfusion abnormalities were detected qualitatively by visual inspection and quantitatively by calculating asymmetry index (AI) maps and significant z-score cluster maps based on successfully operated cases. ASL results were prospectively compared to scalp EEG, structural 3T-MRI, FDG-PET, ictal/interictal SPECT, magnetoencephalography (MEG), and intracranial recording results, as well as the final surgically proven epileptogenic zone (EZ) in operated patients who had at least 1 year of good (Engel class I/II) seizure outcome and positive histopathology results.

RESULTS

Qualitative ASL perfusion abnormalities were found in 17/25 cases (68%), specifically in 17/20 MRI-positive cases (85.0%) and in none of the 5 MRI-negative cases. ASL was concordant with localizing scalp EEG findings in 66.7%, structural 3T-MRI in 90%, FDG-PET in 75%, ictal/interictal SPECT in 62.5%, and MEG in 75% of cases, and with intracranial recording results in 40% of cases. Eleven patients underwent surgery; in all 11 cases the EZ was surgically proven by positive histopathology results and the patient having at least 1 year of good seizure outcome. ASL results were concordant with this final surgically proven EZ in 10/11 cases (sensitivity 91%, specificity 50%). All 10 ASL-positive patients who underwent surgery had positive surgical pathology results and good long-term postsurgical seizure outcome at a mean follow-up of 39 months. Retrospective quantitative analysis based on significant z-score clusters found 1 true-positive result that was missed by qualitative analysis and 3 additional false-positive results (sensitivity 100%, specificity 23%).

CONCLUSIONS

ASL supports the hypothesis regarding the EZ in poorly defined focal epilepsy cases in children. Due to its convenience and noninvasive nature, the authors recommend that ASL be added routinely to the presurgical MRI evaluation of epilepsy. Future optimized quantitative methods may improve the diagnostic yield of this technique.